Study of angiogenic cell therapy for progressive pulmonary arterial hypertension: intervention with repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE trial

Pulmonary arterial hypertension (PAH) is characterized by widespread pruning of the distal pulmonary arterial bed, leading to increased pulmonary vascular resistance, right heart failure, and death. PAH patients receiving background therapy were randomized to receive a course of 4 monthly infusions of placebo or angiogenic endothelial progenitor cells (EPCs) transfected with endothelial NO synthase (eNOS) over the first 6-month period for a cumulative dose of 80 M cells. Due to the COVID-19 pandemic, the trial was stopped after 12 of the planned 45 patients were enrolled (five placebo, seven eNOS-EPCs). While the small sample size precluded appropriately powered analyses, a possible difference was seen in 6MWD between the eNOS-EPC and placebo groups over 6 months, with a greater proportion of patients in the cell therapy group achieving a minimal clinically important increase in 6MWD of 33-m (71.4% vs 40%, respectively). Treatment of PAH patients with a course of 4 monthly infusions of eNOS-EPCs was well tolerated and may have resulted in clinical benefit.